1. Field of the Invention
The present invention is an additive preparation for use in collection devices wherein the additive preparation effervesces when in contact with a body fluid. The additive preparation desirably comprises a formulation comprising an additive such as a clot activator, anticoagulant or urine preservation material, an organic acid, a metal carbonate compound and a surfactant agent which is capable of rendering the surface of a collection device to have properties that cause the surface to repel the adsorption of components of a body fluid sample. The effervescence effect of the formulation aids in dispersal and delivery of the additive and the surfactant agent in a body fluid sample. The formulation is desirably tableted to provide an effective, easily stored and handled preparation. In particular, the formulation of the present invention preferably comprises a clot activator or anticoagulant, an organic acid, a metal carbonate compound, and a surfactant agent wherein the formulation renders the blood collection device hemocompatible and enhances clot activation or the anticoagulant effect in a blood specimen.
2. Description of Related Art
There are many applications in the medical industry where it is desirable to have a blood collection device which has a surface which is hemocompatible. Such devices have surfaces that inhibit the adsorption of blood components such as proteins, red blood cells (RBC) and platelets. xe2x80x9cFoulingxe2x80x9d of the surfaces through such adsorption could render the devices less effective or even ineffective. For example, any cellular material adhering to the wall has the potential to contaminate the serum specimen if the cells lyse and release their contents. Such lysis would contaminate analytes and compromise clinical test results. It is for this reason that evacuated blood collection tubes, in particular plastic serum tubes for which adhesion of blood components to the tube wall is possible, are often coated with a surfactant which minimizes the adsorption of blood components to the wall. Plastic tubes are preferred over glass tubes in that they are resistant to breakage and therefore help to prevent the spreading of bloodborne pathogens. Currently, such plastic tubes are made of polyester (PET) and are often coated with a silicone surfactant and a particulate clot activator material such as silica. In addition to minimizing the adherence of blood components to the tube wall, the silicone surfactant enables better distribution of silica along the tube wall.
The silicone surfactant is generally sprayed onto the inner wall of the plastic tube using water as the carrier. Moreover, where both silica clot activator and silicone surfactant are to provide the coat, they may be sprayed onto the wall using polyvinylpyrrolidone (PVP) and water as the carriers. From a manufacturing stand point, the processes of coating and drying the tube wall are costly in that they are require a long time to complete and are labor-intensive.
Blood collected in evacuated tubes often must be clotted prior to clinical examination because it is desirable to form a dense clot as rapidly and completely as possible to facilitate clean separation of the clot from the serum layer by centrifugation. To achieve this end, both surfactant-coated plastic as well as glass blood collection tubes frequently employ a clot activator. Typical clot activators are diatomaceous earth and particles of inorganic silicates, or biochemicals such as ellagic acid, thrombin, trypsin and thromboplastin.
Typical clot activators used commercially are silica coated on fabric, silica particles in small plastic cups or silicate particles applied to the tube wall with a polyvinylpyrrolidone (PVP) carrier. However, in these type of arrangements, it is necessary for the user to initiate mixing of the sample so that the activator is bioavailable to the specimen thus providing the desired effect of the additive in the sample. Mixing helps to dissolve the PVP in the sample, releasing the silica to create a more uniform dispersion and enabling the silica to be held onto the tube wall. Therefore, the mixing requirement is critical to obtaining the desired effect of the additives.
Maximum effectiveness is achieved by thorough dispersion of the clot activator throughout the blood sample. Since clot activator materials are generally in powder form or as a wall coating, mixing of the clot activator with the blood sample to achieve dispersion may be a physically awkward operation. Also complete dispersion of the clot activator material in the blood sample tends to be frustrated by the tendency of the clot activator material to agglomerate upon moistening.
In addition, agglomerated clot activator particles tend to settle relatively rapidly, according to Stokes Law, which provides that the settling rate of a particle in a dispensing fluid will be governed by its relative diameter and density as well as the fluid""s viscosity and density.
Therefore, there is a need for providing a means for deploying an additive in a body fluid with minimal requirements of the user to initiate mixing of the additive and the body fluid and whereby the additive is able to provide rapid and reliable performance under variable handling conditions.
Moreover, there is a need for providing a means for deploying a surfactant capable of inhibiting the adsorption of body fluid components to a surface of a body fluid collection device with minimal requirements of the user to initiate mixing of the surfactant and the body fluid and whereby the surfactant is able to be rapidly dispersed in the body fluid. One significance of not having to coat the wall prior to collection of a sample is the considerable cost savings by eliminating the long and labor-intensive processes of coating and drying the tube walls.
More particularly, there is a need for a blood collection tube with both means for rendering the surface of the tube hemocompatible at the time a blood sample is collected and means for promoting clot-acceleration of a blood sample which provides an enhanced rate of blood coagulation (shortened time for blood coagulation) without leaving any substantial amount of soluble or particulate material in the serum layer on centrifugation, thus avoiding potential interference with clinical tests, particularly in blood banking procedures. Whereas there are numerous commercial products available that employ clot activators, these products are unable to satisfactorily provide a shortened time for blood coagulation or provide a sample with minimal soluble or particulate material in the serum layer.
The present invention is an additive formulation for use in collection devices wherein the additive preparation effervesces when in contact with a body fluid. The additive preparation desirably comprises a formulation comprising an additive, an organic acid, a metal carbonate compound and surfactant capable of inhibiting the adsorption of components of a body fluid sample to a surface of a body fluid collection device.
It is desirable that the surfactant reduces the surface tension of blood to about 50 dynes/cm.
Desirably, the additive is a clot activator, anticoagulant, urine preservation material or any other body fluid preservative.
In addition, the additive formulation may further comprise a stabilizer and/or a flow improver or a binder.
Desirably, the additive formulation comprises:
(a) from about 40 weight percent to about 90 weight percent of an additive;
(b) from about 5 weight percent to about 30 weight percent of an organic acid or mixtures thereof;
(c) from about 5 weight percent to about 30 weight percent of a metal carbonate compound; and
(d) from about 2 weight percent to about 10 weight percent of a surfactant which is capable of inhibiting the adsorption of compounds of a body fluid to a surface of a body fluid collection device.
The present invention is most preferably an additive formulation for enhancing clot activation of a blood sample. The additive formulation desirably comprises a clot activator, an organic acid and a metal carbonate compound, and a surfactant which is capable of inhibiting the adsorption of blood components to a blood collection device.
Preferably, the clot activator additive formulation comprises:
(a) about 70 weight percent to about 95 weight percent of a clot activator;
(b) about 3 weight percent to about 15 weight percent of organic acid;
(c) about 3 weight percent to about 15 weight percent of metal carbonate; and
(d) about 4 weight percent to about 6 weight percent of a surfactant which is capable of inhibiting the adsorption of blood components to a blood collection device.
The additive formulation may further comprise a binding agent from about 1 weight percent to about 30 weight percent of a binder.
The clot activator may be diatomaceous earth, particles of inorganic silicates or biochemicals such as ellagic acid, thrombin, trypsin and thromboplastin or combinations thereof.
It is preferred that the surfactant is a silicone surfactant capable of reducing the surface tension of blood to about 50 dynes/cm.
A significant attribute of the additive formulation of the present invention is its use in collection devices wherein the additive preparation effervesces when in contact with a body fluid sample. The effect of the additive preparation therefore aids in the dispersal and delivery of both the additive and a surfactant to a body fluid sample. The effervescent dispersal of the surfactant renders the collection device to be compatible with the body fluid sample.
A significant attribute of the clot activator additive formulation of the present invention is its use in blood collection devices as an effective and efficient means for promoting blood coagulation in a collection device which has been made hemocompatible by the presence of a surfactant in the same formulation. Most importantly is that the additive formulation and the blood sample does not have to be mixed by the user.
An important advantage of the clot activator additive formulation of the present invention is its ease of use not requiring lengthy time to promote blood coagulation as compared to conventional techniques.
Furthermore, it is an important advantage of the additive formulation that the inclusion of a surfactant component capable of making a blood evacuated tube hemocompatible eliminates the need for a tube which has been precoated with a surfactant. Therefore, the costly and timely steps of coating and drying these tubes during manufacture thereof can be eliminated.
Notably, the formulations of the present invention rapidly disintegrate and disperse in a body fluid sample, thereby minimizing the requirement that the user assist in mixing the formulation and the body fluid sample.